Pancreatic cancer is one of the most deadly cancers, in part because it is often undetected until an advanced stage. If a patient is diagnosed at a late stage, the survival rate at five years after diagnosis is only about 5 percent. Early diagnosis at an early stage however can lead to significantly improved survival outcome. It is estimated that as many as 10% of pancreatic cancers are familial or hereditary. For familial pancreatic cancer, if a predisposition in a patient having a family history can be detected before cancer develops, then early start of surveillance and screening could increase the chance of early diagnosis and improved prognosis. Five different genetic syndromes have been associated with predisposition to pancreatic cancer. These include BRCA2 mutations, familial atypical multiple mole melanoma (FAMMM), Peutz-Jeghers Syndrome, hereditary pancreatitis, and the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. See e.g., Tascilar et al., Anal. Cell Pathol., 19(3-4):105-10 (1999). However, many familial pancreatic cancer cases can not be explained by any of these five genetic syndromes. Clearly there is a need to identify additional genetic predisposition markers for pancreatic cancer.
Another difficulty in pancreatic cancer is that there is no effective treatment for advanced pancreatic cancer. Gemcitabine, the current standard of care, results in an average progression free survival of 3-4 months and median survival of 5-6 months. See O'Reilly, Gastrointest. Cancer Res., 3(2 Suppl):S11-5 (2009. Second line treatment after gemcitabine failure is even less effective with median survival of approximately 3 months. See, Moore et al., J. Clin. Oncol., 25(15):1960-6 (2007); Philip, Gastrointest. Cancer Res., 2(4 Suppl):S16-9 (2008). One strategy actively sought to improve outcome is to personalize patient treatment. In recent years, with the ability to interrogate the entire human cancer genome, it is becoming apparent that some cancers can be effectively treated by targeting specific somatic genetic alterations present in the cancers. This is perhaps best exemplified by the observation that patients with lung cancer harboring mutations in the epidermal growth factor (EGFR) gene respond rather dramatically to agents that target this receptor. Lynch et al., N. Engl. J. Med., 350(21):2129-39 (2004); Paez et al., Science, 304(5676):1497-500 (2004). Clearly, there is also a need for biomarkers predictive of therapy outcome and useful in personalized pancreatic cancer treatment.